Month: March 2012

The Oxford University spin-out Oxford Nanopore Technologies created a stir last month by announcing that it would be bringing to market this year systems to read out the sequence of individual DNA molecules by threading them through nanopores. It’s claimed that this will allow a complete human genome to be sequenced in about 15 minutes for a few thousand dollars; the company also is introducing a cheap, disposable sequencer which will sell for less that $900. Speculation has now begun about the future of the company, with valuations of $1-2 billion dollars being discussed if they decide to take the company public in the next 18 months.

It’s taken a while for this idea of sequencing a single DNA molecule by directly reading out its bases to come to fruition. The original idea came from David Deamer and Harvard’s Dan Branton in the mid-1990s; from Hagen Bayley, in Oxford, came the idea of using an engineered derivative of a natural pore-forming protein to form the hole through which the DNA is threaded. I’ve previously reported progress towards this goal here, in 2005, and in more detail here, in 2007. The Oxford Nanopore announcement gives us some clues as to the key developments since then. The working system uses a polymer membrane, rather than a lipid bilayer, to carry the pore array, which undoubtedly makes the system much more robust. The pore is still created from a pore forming protein, though this has been genetically engineered to give greater discrimination between different combinations of bases as the DNA is threaded through the hole. And, perhaps most importantly, an enzyme is used to grab DNA molecules from solution and feed them through the pore. In practise, the system will be sold as a set of modular units containing the electronics and interface, together with consumables cartridges, presumably including the nanopore arrays and the enzymes. The idea is to take single molecule analysis beyond DNA to include RNA and proteins, as well as various small molecules, with a different cartridge being available for each type of experiment. This will depend on the success of their program to develop a whole family of different pores able to discriminate between different types of molecules.

What will the impact of this development be, if everything works as well as is being suggested? (The prudent commentator should stress the if here, as we haven’t yet seen any independent trials of the technology). Much has already been written about the implications of cheap – less than $1000 – sequencing of the human genome, but I can’t help wondering whether this may not actually be the big story here. And in any case, that goal may end being reached with or without Oxford Nanopore, as this recent Nature News article makes clear. We still don’t know whether the Oxford Nanopore technique will be yet competitive on accuracy and price with the other contending approaches. I wonder, though, whether we are seeing here something from the classic playbook for a disruptive innovation. The $900 device in particular looks like it’s intended to create new markets for cheap, quick and dirty sequencing, to provide an income stream while the technology is improved further – with better, more selective pores and better membranes (inevitably, perhaps, Branton’s group at Harvard reported using graphene membranes for threading DNA in Nature last year). As computers continue to get faster, cheaper and more powerful, the technology will automatically benefit from these advances too – fragmentary and perhaps imperfect sequence information has much greater value in the context of vast existing sequence libraries and the data processing power to use them. Perhaps applications for this will be found in forensic and environmental science, diagnostics, microbiology and synthetic biology. The emphasis on molecules other than DNA is interesting too; single molecule identification and sequencing of RNA opens up the possibility of rapidly identifying what genes are being transcribed in a cell at a given moment (the so-called “transcriptome”).

The impact on the investment markets for nanotechnology is likely to be substantial. Existing commercialisation efforts around nanotechnology have been disappointing so far, but a company success on the scale now being talked about would undoubtedly attract more money into the area – perhaps it might also persuade some of the companies currently sitting on huge piles of cash that they might usefully invest some of this in a little more research and development. What’s significant about Oxford Nanopore is that it is operating in a sweet spot between the mundane and the far-fetched. It’s not a nanomaterials company, essentially competing in relatively low margin speciality chemicals, nor is it trying to make a nanofactory or nanoscale submarine or one of the other more radical visions of the nanofuturists. Instead, it’s using the lessons of biology – and indeed some of the components of molecular biology – to create a functional device that operates on the true single molecule level to fill real market needs. It also seems to be displaying a commendable determination to capture all the value of its inventions, rather than licensing its IP to other, bigger companies.

Finally, not the least of the impacts of a commercial and technological success on the scale being talked about would be on nanotechnology itself as a discipline. In the last few years the field’s early excitement has been diluted by a sense of unfulfilled promise, especially, perhaps, in the UK; last year I asked “Why has the UK given up on nanotechnology?” Perhaps it will turn out that some of that disillusionment was premature.